title: Effects of subinhibitory concentrations of antimicrobial agents on Escherichia coli O157:H7 Shiga toxin release and role of the SOS response.
abstract: Treatment of Escherichia coli O157:H7 by certain antimicrobial agents often exacerbates the patient's condition by increasing either the release of preformed Shiga toxins (Stx) upon cell lysis or their production through the SOS response-triggered induction of Stx-producing prophages. Recommended subinhibitory concentrations (sub-MICs) of azithromycin (AZI), gentamicin (GEN), imipenem (IMI), and rifampicin (RIF) were evaluated in comparison to norfloxacin (NOR), an SOS-inducer, to assess the role of the SOS response in Stx release. Relative expression of recA (SOS-inducer), Q (late antitermination gene of Stx-producing prophage), stx1, and stx2 genes was assessed at two sub-MICs of the antimicrobials for two different strains of E. coli O157:H7 using reverse transcription-real-time polymerase chain reaction. Both strains at the two sub-MICs were also subjected to Western blotting for LexA protein expression and to reverse passive latex agglutination for Stx detection. For both strains at both sub-MICs, NOR and AZI caused SOS-induced Stx production (high recA, Q, and stx2 gene expression and high Stx2 production), so they should be avoided in E. coli O157:H7 treatment; however, sub-MICs of RIF and IMI induced Stx2 production in an SOS-independent manner except for one strain at the first twofold dilution below MIC of RIF where Stx2 production decreased. Moreover, GEN caused somewhat increased Stx2 production due to its mode of action rather than any effect on gene expression. The choice of antimicrobial therapy should rely on the antimicrobial mode of action, its concentration, and on the nature of the strain.
authors.affiliation: Department of Experimental Pathology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Farah J
authors.initials: FJ
authors.lastname: Nassar
authors.forename: Elias A
authors.initials: EA
authors.lastname: Rahal
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sabra
authors.forename: Ghassan M
authors.initials: GM
authors.lastname: Matar
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D019453:Escherichia coli O157 / Q000187:drug effects / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007841:Latex Fixation Tests; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D039002:Prophages / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology; D013014:SOS Response, Genetics; D022621:Shiga Toxin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D005839:Gentamicins; D015378:Imipenem; D022621:Shiga Toxin; D017963:Azithromycin; D009643:Norfloxacin; D012293:Rifampin